Cellular Localization of gdnf in Adult Zebrafish Brain

Abstract

Glial cell line-derived neurotrophic factor (GDNF) was initially described as important for dopaminergic neuronal survival and is involved in many other essential functions in the central nervous system. Characterization of GDNF phenotype in mammals is well described; however, studies in non-mammalian vertebrate models are scarce. Here, we characterized the anatomical distribution of gdnf-expressing cells in adult zebrafish brain by means of combined in situ hybridization (ISH) and immunohistochemistry. Our results revealed that gdnf was widely dispersed in the brain. gdnf transcripts were co-localized with radial glial cells along the ventricular area of the telencephalon and in the hypothalamus. Interestingly, Sox2 positive cells expressed gdnf in the neuronal layer but not in the ventricular zone of the telencephalon. A subset of GABAergic precursor cells labeled with dlx6a-1.4kbdlx5a/6a: green fluorescence protein (GFP) in the pallium, parvocellular preoptic nucleus, and the anterior and dorsal zones of the periventricular hypothalamus also showed expression with gdnf mRNA. In addition, gdnf signals were detected in subsets of dopaminergic neurons, including those in the ventral diencephalon, similar to what is seen in mammalian brain. Our work extends our knowledge of gdnf action sites and suggests a potential role for gdnf in adult brain neurogenesis and regeneration.

gdnf affects early diencephalic dopaminergic neuron development through regulation of differentiation‐associated transcription factors in zebrafish

“…Defects in Gdnf were shown to affect the development of enteric neurons in both Gdnfnull mice (Sánchez et al, 1996) and zebrafish morphants (Shepherd et al, 2001). Consistent to what has been previously reported in the adult rat brain (Barroso-Chinea et al, 2005), we similarly observed gdnf co-expression in TH-immunoreactive neurons in a subset dopaminergic neuron clusters in the vDC (Wong et al, 2020). It is as yet unclear what the relationship is between gdnf and the dopaminergic system in zebrafish.…”

“…Likewise, WISH has shown that zebrafish gdnf expression is widespread in the brain and enteric system at various stages of embryonic development (Lucini et al, 2008;Reichenbach et al, 2008;Wong et al, 2020). Expression patterns of gdnf suggest a prominent role for gdnf in zebrafish embryonic development.…”

“…The results showed that gdnf expression was widely dispersed in the brain with its transcripts found in early committed F I G U R E 6 Altered expression of dopaminergic neuron fate-associated transcription factors in gdnfdeficient larvae. (a-i) qRT-PCR profiling of transcription factors at 1, 3, and 7 dpf (n number is indicated in each bar of the graph, a pool of 10 larvae per n, by multiple t test, *p < .05, ** p < .01, ***p < .001) progenitor cells as well as mature neurons, including in dopaminergic neurons (Wong et al, 2020). As gdnf is expressed in zebrafish larvae and in the adult brain (Lucini et al, 2008;Reichenbach et al, 2008; Wong et al, 2020), we were keen to characterize the function of gdnf in zebrafish, particularly in the ventral diencephalon (vDC) dopaminergic neurons.…”

Mechanical Brain Injury Increases Cells’ Production of Cystathionine β-Synthase and Glutamine Synthetase, but Reduces Pax2 Expression in the Telencephalon of Juvenile Chum Salmon, Oncorhynchus keta

“…However, studies show that neuronal precursors in the zebrafish telencephalon are characterized by spatial heterogeneity [ 4 ]. Previous studies on zebrafish revealed a granular pattern of expression for glial cell-derived neurotrophic factor (GDNF), which is believed to be involved in neurogenesis and neuronal regeneration [ 30 ]. An analysis of our data concerning the morphometric and densitometric parameters of GS + cells in the pallium of juvenile chum salmon confirmed the heterogeneous pattern of labeled NPCs.…”

Neuroprotective effects of Neurotrophin-3 in MPTP-induced zebrafish Parkinson’s disease model

“…Some regions have exceptions, such as in the OB where ntf3 was abundant in the ECL, while bdnf mRNA was found more abundantly in the glomerular layer of the OB. On the other hand, gdnf , although it has abundant expression in the ECL similar to ntf3, but it was sparsely expressed in the PT region, unlike ntf3 ( Wong et al, 2020 ). Similar to bdnf , our study also observed that ntf3 mRNA was expressed in neurons and not glial cells ( Cacialli et al, 2016 ; Anand and Mondal, 2020 ), but gdnf was more abundantly expressed in glial cells compared to the neuronal marker ( Wong et al, 2020 ).…”